Search Results

cobas® BKV is an in vitro nucleic acid amplification test for the quantitation of BK virus (BKV) DNA in human EDTA plasma on the cobas® 6800/8800 Systems.

cobas® BKV is intended for use as an aid in the management of BKV in transplant patients. In patients undergoing monitoring of BKV, serial DNA measurements can be used to indicate the need for potential treatment changes and to assess viral response to treatment.

The results from cobas® BKV are intended to be read and analyzed by a qualified licensed healthcare professional in conjunction with clinical signs and symptoms and relevant laboratory findings. Test results must not be the sole basis for patient management decisions.

cobas® BKV is not intended for use as a screening test for blood products or human cells, tissues, and cellular and tissue-based products (HCT/Ps).

cobas® BKV is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as either target not detected, BKV DNA detected < LLoQ (lower limit of quantitation), BKV DNA detected > ULoQ (upper limit of quantitation), or a value in the linear range LLoQ < x < ULoQ. Results can be reviewed directly on the system screen, exported, or printed as a report.

Nucleic acid from patient samples and added lambda DNA-QS molecules is simultaneously extracted. In summary, viral nucleic acid is released by addition of proteinase and lysis reagent to the sample. The released nucleic acid binds to the silica surface of the added magnetic glass particles. Unbound substances and impurities, such as denatured protein, cellular debris and potential PCR inhibitors are removed with subsequent wash reagent steps and purified nucleic acid is eluted from the glass particles with elution buffer at elevated temperature.

Selective amplification of target nucleic acid from the sample is achieved by the use of a dual target virus specific approach from highly-conserved regions of the BKV located in the BKV small t-antigen region and the BKV VP2 region. Selective amplification of DNA-QS is achieved by the use of sequence-specific forward and reverse primers which are selected to have no homology with the BKV genome. A thermostable DNA polymerase enzyme is used for amplification. The target and DNA-QS sequences are amplified simultaneously utilizing a universal PCR amplification profile with predefined temperature steps and number of cycles. The master mix includes deoxyuridine triphosphate (dUTP), instead of deoxythimidine triphosphate (dTTP), which is incorporated into the newly synthesized DNA (amplicon). Any contaminating amplicon from previous PCR runs is eliminated by the AmpErase enzyme, which is included in the PCR mix, when heated in the first thermal cycling step. However, newly formed amplicons are not eliminated since the AmpErase enzyme is inactivated once exposed to temperatures above 55°C.

The cobas® BKV master mix contains two detection probes specific for BKV target sequences and one for the DNA-QS. The probes are labeled with target-specific fluorescent reporter dyes allowing simultaneous detection of BKV target and DNA-QS in two different target channels. The fluorescent signal of the intact probes is suppressed by the quencher dye. During the PCR amplification step, hybridization of the specific single-stranded DNA templates results in cleavage by the 5'-to-3' nuclease activity of the DNA polymerase resulting in separation of the reporter and quencher dyes and the generation of a fluorescent signal. With each PCR cycle, increasing amounts of cleaved probes are generated and the cumulative signal of the reporter dye is concomitantly increased. Real-time detection and discrimination of PCR products are accomplished by measuring the fluorescence of the released reporter dyes for the viral targets and DNA-QS.

The provided document is a 510(k) Summary for the cobas® BKV test for use on the cobas® 6800/8800 Systems. This document focuses on demonstrating substantial equivalence to a predicate device through non-clinical performance evaluation, rather than an AI/ML device requiring a comparative effectiveness study with human readers. Therefore, several of the requested sections (e.g., sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, ground truth for test set, training set details) are not directly applicable or explicitly stated in the context of this In Vitro Diagnostic (IVD) device submission for a quantitative nucleic acid amplification test.

However, I will extract relevant information to address the applicable criteria based on the provided text.

Acceptance Criteria and Device Performance for cobas® BKV

The acceptance criteria for this diagnostic device are primarily defined by various performance characteristics required for quantitative viral nucleic acid tests. The study proves the device meets these criteria through a series of non-clinical performance evaluations.

Table of Acceptance Criteria and Reported Device Performance

Study Details:

1. Sample Size and Data Provenance:

   • Test Set (Clinical Concordance): 550 valid samples (217 neat clinical, 303 diluted clinical derived from 129 transplant subjects, and 30 contrived samples).
   • Provenance: Clinical samples were from BKV infected and non-infected patients. Although not explicitly stated, the context of an FDA submission for an IVD test likely implies data collected under controlled conditions at testing sites, potentially from multiple geographical locations if a multi-site study was conducted (the Reproducibility study specified 3 testing sites). The samples included both retrospective (stored clinical samples) and prospective (contrived samples) elements.
   • Non-Clinical Studies: Sample sizes vary by test as detailed in the table (e.g., 63 replicates per level for LoD, 36 replicates per panel member for linear range, 72 replicates per level for precision, 240/225 replicates for cross-contamination, 270 valid tests per concentration for reproducibility).

2. Number of Experts and Qualifications: Not applicable. This is an IVD device for quantitative viral DNA measurement, not an AI/ML device for image interpretation or diagnosis by experts. Ground truth is established analytically (e.g., known concentrations of viral standards) or through comparison to a well-established laboratory method.

3. Adjudication Method: Not applicable. For IVD tests like this, objective analytical measurements are compared rather than subjective interpretations needing adjudication.

4. MRMC Comparative Effectiveness Study: No. This is an In Vitro Diagnostic (IVD) quantitative nucleic acid amplification test, not an AI-assisted diagnostic imaging device that involves human readers. The standard of comparison is against a well-established laboratory method (LDT) and analytical performance targets, not human reader improvement.

5. Standalone Performance: Yes, the entire document describes the standalone performance of the cobas® BKV assay. The device measures BKV DNA concentration directly without human-in-the-loop assistance for the measurement itself, though a qualified healthcare professional interprets the results in a clinical context.

6. Type of Ground Truth Used:

   • Analytical/Reference Standards: For LoD, linearity, traceability, precision, and specificity, the ground truth was established using known concentrations of the 1st WHO International Standard for BK Virus DNA (NIBSC 14/212), armored DNA for specific subgroups/subtypes, and well-characterized high titer BKV DNA (subgroup Ib).
   • Comparative Method: For clinical concordance, the ground truth was established by comparing results from the cobas® BKV test to those from a well-established laboratory developed nucleic acid test (LDT) from Indiana University (referred to as "comparator BKV LDT"). This LDT results served as the reference for comparison and agreement.

7. Sample Size for Training Set: Not applicable. This is a molecular diagnostic assay characterized through analytical and clinical performance studies, not an AI/ML model that undergoes a distinct training phase with a dedicated training set. The "training" of the assay involves its development and optimization based on scientific principles of nucleic acid amplification and detection, and then validated through the studies described.

8. How Ground Truth for Training Set was Established: Not applicable, as there isn't a "training set" in the AI/ML sense. The development of the assay (analogous to training) would rely on molecular biology knowledge, optimization experiments, and characterization against internally developed standards and reference materials, ultimately ensuring performance against defined analytical targets and external standards (like the WHO standard).

Ask a specific question about this device